Science Objectives for Everyone
The Commercial Protein Crystal Growth HM (CPCG-HM) investigation expands an ongoing program into the complex realm of membrane proteins that move signals or molecules to and from a cell’s interior or help cells identify each other for immune responses. Proteins in the microgravity environment are exposed to conditions that concentrate them so they form crystals that would be too fragile to form on Earth, but which can be returned to Earth for X-ray analysis.

Science Results for EveryoneInformation Pending

The following content was provided by Lawrence J. DeLucas, Ph.D., O.D., and is maintained in a database by the ISS Program Science Office.

Experiment Details

OpNom:

Principal Investigator(s)

Lawrence J. DeLucas, Ph.D., O.D., University of Alabama at Birmingham, Birmingham, AL, United States

Co-Investigator(s)/Collaborator(s)

Alexander McPherson, Ph.D., University of California, Irvine, Irvine, CA, United States

Joseph D. Ng, Ph.D., iXpressGenes, Hunstville, AL, United States

Developer(s)University of Alabama at Birmingham, Birmingham, AL, United States

To conclusively demonstrate the effect of microgravity on the size and quality of crystals for a variety of high-value proteins.

Upon completion for the experiments it will be demonstrated that microgravity protein crystallization provided an improvement over ground controlled crystallization.

Improved space grown protein crystals will provide three-dimensional x-ray crystallographic structures for several high valued proteins. Eventually these structures will help researchers determine how specific proteins function and are involved in the disease process. Numerous drugs today are the product of this structured based drug design.

Description

Proteins are important macromolecules without which our bodies would be unable to repair, regulate, or protect themselves. The use of X-ray crystallography to determine protein structure requires the production of well-ordered protein crystals that are of sufficient quality. Without high quality crystals of a protein, it is impossible to carry out crystallographic structural studies. Using three-dimensional structure information, researchers can determine how proteins function and in cases where these proteins are involved in disease processes, the structure is often used to design new drugs that specifically interact with the protein. Many leading drugs today are the product of structure-based drug design. In microgravity, the elimination of sedimentation and convection produces a highly unique environment for space-based experiments such as protein crystallization. The human body contains over 100,000 proteins that play important roles in the everyday function of the body such as the formation of major components of muscle and skin, and how the body fights diseases. In order to fully understand the function of proteins, three-dimensional structural information becomes necessary. The Structure of individual proteins can be studied with the growth of high quality crystals in which the molecules of the protein are arranged in a regular, repeating pattern. In order to produce high-quality crystals of a protein, it must be reasonably pure with respect to other contaminating proteins, it must be homogeneous and it's three-dimensional conformation relatively stable. Crystallization occurs in aqueous solution when purified protein molecules are coaxed to slowly self-associate, through relatively weak interactions such as ionic or hydrogen bonds. Individual protein molecules align themselves in a repeating series of "unit cells" by adopting a consistent orientation that eventually forms a crystal with sharp facets. Protein crystallization serves as the basis for X-ray crystallography, wherein a crystallized protein is used to determine the protein’s three-dimensional structure via x-ray diffraction.

While enormous strides have been made in the last decade, there remain a large number of important proteins where the difficulty of obtaining high-quality crystals is the chief barrier to their structural analysis. One class of proteins, membrane proteins, comprises a number of targets identified by the pharmaceutical industry as high-value commercial opportunities (membrane proteins were the targets for approximately 67% of all past marketed drugs and it is estimated that they will comprise targets for an equal percentage of all future drugs)[1]. Membrane protein crystallization represents one area where the onset of space commercialization can maximize the impact of the microgravity environment in space-based research applications for the academic, government and pharmaceutical industry. Other areas include high-value aqueous proteins and protein complexes (based on their functional importance in biological systems) many of which have yielded crystals of poor quality (thus far microgravity crystallization has been attempted on only 3 membrane proteins and two protein complexes). Access to unique data optimized in microgravity could have great relevance for understanding protein structures and advancing new drugs into the pharmaceutical market.
Crystal growth in a microgravity environment can have beneficial effects on the size and more importantly, the intrinsic order of these protein crystals. Membrane proteins and large aqueous proteins or protein complexes typically diffract poorly and exhibit high mosaicity.

Significant disadvantages of past microgravity flights include the short mission duration (the majority of the past data was collected on spatial flights with mission durations of two weeks or less). The results of the program, while intriguing, had a limited impact on structural biology during a time when technological innovations on the ground have produced significant and fundamental advances in our understanding of protein function. However, despite the increased sophistication of ground-based protein crystallization projects, the crystals of a large number of important targets today still have suboptimal diffraction characteristics. Even a slight improvement in diffraction data would have a significant impact on scientist’s ability to use the resulting structures to provide important insights into biological mechanisms.

Space Applications
While Earth-based protein crystal studies have made significant advances in recent years; details of large, key membrane proteins remain hidden in X-ray studies. Even with modest improvements from crystals grown in space without the defects caused by gravity, should allow significant advances in understanding their structure and how they function.

Earth Applications
High-density membrane proteins are targeted for about two-thirds of the current and anticipated pharmaceutical market. Pure crystals that yield information about the protein’s structure will open the way for a coherent, structure-based design of a broader range of medicines for treating diseases and disorders.